White matter hyperintensity spatial patterns: risk factors and clinical correlates

Abstract

AbstractINTRODUCTIONWhite matter hyperintensities (WMH), a major cerebral small vessel disease marker, may arise from different pathologies depending on their location. We explored clinical and genetic correlates of agnostically derived spatial WMH patterns in two longitudinal population-based cohorts (3C-Dijon, LIFE-Adult).METHODSWe derived seven WMH spatial patterns using Bullseye segmentation in 2,736 individuals aged 65+ and explored their associations with vascular and genetic risk factors, cognitive performance, dementia and stroke incidence.RESULTSWMH in the fronto-parietal and anterior periventricular region were associated with blood pressure traits, WMH genetic risk score (GRS), baseline and decline in general cognitive performance, incident all-cause dementia and ischemic stroke. Juxtacortical-deep occipital WMH were not associated with vascular risk factors and WMH GRS, but with incident all-cause dementia and intracerebral hemorrhage.CONCLUSIONAccounting for WMH spatial distribution is key to decipher mechanisms underlying cerebral small vessel disease subtypes, an essential step towards personalized therapeutic approaches.HighlightsWe studied spatial patterns of white matter hyperintensities in 2736 participantsBlood pressure was associated with fronto-parietal and anterior periventricular WMHAnterior periventricular WMH predicted dementia and stroke riskJuxtacortical-deep occipital WMH burden was not associated with blood pressure or WMH genetic riskJuxtacortical-deep occipital WMH predicted dementia and intracerebral hemorrhage.Research in contextSystematic Review: We performed a literature search using PubMed and Google Scholar. Most literature focuses on risk factors and outcomes for total WMH volume. Existing approaches to study WMH spatial patterns are heterogenous and often performed in single cohorts only.Interpretation: Across two independent cohorts of older community-dwelling individuals, we show that WMH in the anterior periventricular and juxtacortical-deep occipital WMH show differential associations with risk factors and clinical outcomes. Anterior periventricular WMH were associated with blood pressure (BP) traits, WMH genetic risk, cognitive performance, dementia and incident stroke. Juxtacortical-deep occipital WMH did not relate to BP or WMH genetic risk and were predictive of dementia and intracerebral hemorrhage. These findings are important for characterizing small vessel disease subtypes and developing targeted prevention and therapeutic strategies.Future Directions: Additional research is warranted to validate these findings and relate them to underlying vascular pathologies.